Background: Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) and adjuvant chemotherapy is a therapeutic choice for women with advanced ovarian cancer. Whether NACT affects the tumor’s molecular profile has not been determined. Methods: This was a retrospective study of patients with advanced-stage epithelial ovarian cancer treated with NACT at oncology departments affiliated with the Hellenic Cooperative Oncology Group (HeCOG). Tumor molecular profiling was performed on formalin-fixed and paraffin-embedded (FFPE) tumor pre- and post-NACT tissues. Homologous recombination deficiency (HRD), tumor-infiltrating lymphocytes (TILs), tumor molecular alterations, and tumor mutational burden (TMB) via next-generation sequencing analysis were assessed. Results: Overall, tumors from 36 patients were assessed, and molecular profiling was evaluated in 20 paired tumor samples. HRD positivity exhibited no significant change between pre- and post-NACT tumors. The BRCA1/2 mutational status remained constant, irrespective of the treatment administration. Pre-NACT tumors tended to exhibit a lower percentage of intratumoral TILs compared to post-NACT tumors (p= 0.004). Differences in the mutation profile between pre- and post-treatment tissue were observed in 33.33% (6/18) of the cases. The mean tumor cell content (TCC) (p-value: 0.0840) and the mean genomic instability score (p-value: 0.0636) decreased slightly numerically after therapy. A moderate inverse relationship was observed between the pre-NACT TMB and the chemotherapy response score (p-value: 0.038), indicating this correlation is statistically significant. Conclusion: This study provides insights into the effect of NACT on the tumor molecular landscape. While BRCA1/2 and HRD status remained stable, an increase in TIL proportion and changes in the mutational profiles were observed post-treatment.
背景：对于晚期卵巢癌患者，新辅助化疗（NACT）后进行间歇性肿瘤细胞减灭术（IDS）及辅助化疗是一种治疗选择。NACT是否影响肿瘤的分子特征尚未明确。方法：本研究回顾性分析了在希腊肿瘤合作研究组（HeCOG）附属肿瘤科接受NACT治疗的晚期上皮性卵巢癌患者。对NACT前后经福尔马林固定、石蜡包埋（FFPE）的肿瘤组织进行了分子特征分析，评估了同源重组缺陷（HRD）、肿瘤浸润淋巴细胞（TILs）、肿瘤分子改变以及通过二代测序分析的肿瘤突变负荷（TMB）。结果：共评估了36例患者的肿瘤，并对20对配对肿瘤样本进行了分子特征分析。HRD阳性在NACT前后肿瘤中未显示显著变化。无论是否接受治疗，BRCA1/2突变状态均保持稳定。与NACT后肿瘤相比，NACT前肿瘤的瘤内TILs比例往往较低（p=0.004）。在33.33%（6/18）的病例中观察到治疗前后组织突变谱存在差异。治疗后，平均肿瘤细胞含量（TCC）（p值：0.0840）和平均基因组不稳定性评分（p值：0.0636）在数值上略有下降。NACT前TMB与化疗反应评分呈中度负相关（p值：0.038），表明该相关性具有统计学意义。结论：本研究揭示了NACT对肿瘤分子特征的影响。虽然BRCA1/2和HRD状态保持稳定，但治疗后观察到TIL比例增加以及突变谱发生变化。
肿瘤(癌症)患者之家